Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2

Ankita Ray; Thu Thi Minh Tran; Rita dos Santos Natividade; Rodrigo A. Moreira; Joshua D. Simpson; Danahe Mohammed; Melanie Koehler; Simon J. L Petitjean; Qingrong Zhang; Fabrice Bureau; Laurent Gillet; Adolfo B. Poma; David Alsteens

doi:10.1021/acsnanoscienceau.3c00060

Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2

Ankita Ray (First Author), Thu Thi Minh Tran (Co-Author), Rita dos Santos Natividade (Co-Author), Rodrigo A. Moreira (Co-Author), Joshua D. Simpson (Co-Author), Danahe Mohammed (Co-Author), Melanie Koehler (Co-Author), Simon J. L Petitjean (Co-Author), Qingrong Zhang (Co-Author), Fabrice Bureau (Co-Author), Laurent Gillet (Co-Author), Adolfo B. Poma^* (Co-Author), David Alsteens^* (Last Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.

Original language	English
Pages (from-to)	136-145
Number of pages	10
Journal	ACS Nanoscience Au
Volume	4
Issue number	2
DOIs	https://doi.org/10.1021/acsnanoscienceau.3c00060
State	Published - 17 Apr 2024
Externally published	Yes

Keywords

ACE2
Atomic force microscopy
RBD
SARS-CoV-2
Steered molecular dynamics
biolayer interferometry
convalescent patient sera

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10.1021/acsnanoscienceau.3c00060

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Ray, A., Minh Tran, T. T., Santos Natividade, R. D., Moreira, R. A., Simpson, J. D., Mohammed, D., Koehler, M., L Petitjean, S. J., Zhang, Q., Bureau, F., Gillet, L., Poma, A. B., & Alsteens, D. (2024). Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2. ACS Nanoscience Au, 4(2), 136-145. https://doi.org/10.1021/acsnanoscienceau.3c00060

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title = "Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2",

abstract = "The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.",

keywords = "ACE2, Atomic force microscopy, RBD, SARS-CoV-2, Steered molecular dynamics, biolayer interferometry, convalescent patient sera",

author = "Ankita Ray and \{Minh Tran\}, \{Thu Thi\} and \{Santos Natividade\}, \{Rita dos\} and Moreira, \{Rodrigo A.\} and Simpson, \{Joshua D.\} and Danahe Mohammed and Melanie Koehler and \{L Petitjean\}, \{Simon J.\} and Qingrong Zhang and Fabrice Bureau and Laurent Gillet and Poma, \{Adolfo B.\} and David Alsteens",

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year = "2024",

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doi = "10.1021/acsnanoscienceau.3c00060",

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Ray, A, Minh Tran, TT, Santos Natividade, RD, Moreira, RA, Simpson, JD, Mohammed, D, Koehler, M, L Petitjean, SJ, Zhang, Q, Bureau, F, Gillet, L, Poma, AB & Alsteens, D 2024, 'Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2', ACS Nanoscience Au, vol. 4, no. 2, pp. 136-145. https://doi.org/10.1021/acsnanoscienceau.3c00060

TY - JOUR

T1 - Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2

AU - Ray, Ankita

AU - Minh Tran, Thu Thi

AU - Santos Natividade, Rita dos

AU - Moreira, Rodrigo A.

AU - Simpson, Joshua D.

AU - Mohammed, Danahe

AU - Koehler, Melanie

AU - L Petitjean, Simon J.

AU - Zhang, Qingrong

AU - Bureau, Fabrice

AU - Gillet, Laurent

AU - Poma, Adolfo B.

AU - Alsteens, David

PY - 2024/4/17

Y1 - 2024/4/17

N2 - The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.

AB - The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.

KW - ACE2

KW - Atomic force microscopy

KW - RBD

KW - SARS-CoV-2

KW - Steered molecular dynamics

KW - biolayer interferometry

KW - convalescent patient sera

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U2 - 10.1021/acsnanoscienceau.3c00060

DO - 10.1021/acsnanoscienceau.3c00060

M3 - Article

AN - SCOPUS:85187492121

SN - 2694-2496

VL - 4

SP - 136

EP - 145

JO - ACS Nanoscience Au

JF - ACS Nanoscience Au

IS - 2

ER -

Single-Molecule Investigation of the Binding Interface Stability of SARS-CoV-2 Variants with ACE2

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Keywords

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